tbuckley/cabot-search huggingface dataset:
Clinical outcomes in COVID-19 patients with cancer who are treated with chemo- or immunotherapy.
Authors: Haris Hatic, Jenny B Jung, Kristine Ria Hearld, Jessy Deshane, Devika Govind Das
Journal: Journal of Clinical Oncology (2022)

e18699 Background: Cancer patients infected with COVID-19 are very vulnerable to increased complications and mortality while actively being treated with chemotherapy or immune checkpoint inhibitors (ICIs). The full impact of COVID-19 infections on this subset of patients has not been fully defined. Our goal was to track clinical outcomes in patients with an underlying malignancy and COVID-19 infection who received chemotherapy or ICIs. Methods: We performed a retrospective chart review of 121 patients (age &gt; 18 years) at the University of Alabama-Birmingham from January 2020 till November 2021 with an advanced solid malignancy that were treated with chemotherapy or ICIs within 12 months of their COVID-19 diagnosis. The aim of this study was to track clinical outcomes including: hospitalization rates, ICU admissions, treatments, and deaths of any cause. Results: A total of 121 patients were examined in this study and 61 received immunotherapy treatment within 12 months. The median age at diagnosis for the ICI group was 62.3 years and 54% were male while for the patients that receive chemotherapy the median age at diagnosis was 65.1 years and 53% were male (Table1). The 3 most common cancers represented in the ICI cohort were lung (30%, NSCLC), liver (13%, HCC) and renal (11%, RCC). While in the chemotherapy group, the 3 most cancers were NSCLC (40%), HCC (12%,), and head &amp; neck (10%, H&amp;N). 25% of patients on ICIs died while only 13% of patients died post chemotherapy. Of the ICI patients that died, 33% were admitted to the intensive care unit (ICU) and 53% received oxygen, steroids and antiviral therapy. For the chemotherapy patients that died, 25% were admitted to the ICU and 50% received oxygen, steroids and antiviral therapy. Patients with lower ECOG (0.98) had lower mortality compared to patients with worse functional status (0.98 vs 1.52; t = 3.20; p &lt; 0.01). Factors associated with increased admission were higher ECOG (1.07 vs 1.67; f = 3.05; p = 0.05), higher AST (21.2 vs 40.9, f = 10.2; p &lt; 0.001), lower absolute lymphocyte count (1122.8 vs 408.9, f = 5.99; p &lt; 0.01) and higher oxygen needs (0.02 vs 1.11, f = 29.5; p &lt; 0.001). Conclusions: ICI mortality was higher compared to patients receiving chemotherapy, especially for those with reduced functional status. Factors for hospitalization included: higher ECOG, higher AST, lower lymphocyte count and increased oxygen needs. However, further investigation still needs to be undertaken to understand if the PD-1-PD-L1 pathway with the subsequent inflammatory cascade post COVID-19 can impact overall survival.[Table: see text]
Immune phenotypes and T-cell density at the invasive margin correlate with prognosis in epithelial vulvar cancer.
Authors: E C Burandt, Niclas Blessin, Ann-Christin Rolschewski, Florian Lutz, Tim Mandelkow, Cheng Yang, Elena Bady, Viktor Reiswich, Ronald Simon, Guido Sauter, Sven Mahner, Nikolaus de Gregorio, Rüdiger Klapdor, Matthias Kalder, Ioana Braicu, Sophie Fuerst, Maximillian Klar, Hans-Georg Strauss, Katharina Prieske, Linn Lena Woelber
Journal: Journal of Clinical Oncology (2022)

5599 Background: Tumor infiltrating lymphocytes (TILs) in the cancer microenvironment are of prognostic value in many solid tumors. However, only little is known about TILs infiltration and its predictive value in vulvar cancer. Methods: Immunohistochemistry and automated digital image analysis was applied to measure the densities of CD3 + (DAKO, Santa Clara, US; #IR503) and CD8 + (DAKO, Santa Clara, US; #IR623) TILs at the invasive margin (IM) and in the center of 530 vulvar carcinomas. Results: At the IM the mean immune cell density was significantly higher compared to the center of the tumor (CD3: 1772±1105, CD8: 769±644 cells/mm 2 vs. CD3: 518±570, CD8: 301±445 cells/mm 2 , p≤0.0001). An elevated density of CD3 + T-cell at the IM was significantly associated with low tumor stage (p = 0.0012). The 2-years OS and PFS rate was significantly different between the group with a high (OS: 82%, PFS: 65%), moderate (OS: 76%, PFS: 55%), or low CD3 + T-cell density at the IM (OS: 64%, p = 0.008, PFS: 44%, p = 0.02). The prognostic impact of CD3 + cells in the center of the tumor was weaker compared to the IM (OS p = 0.046, PPS p = 0.031) and lacking for CD8 + T-cell densities at any location (p≥0.14 each). Unsupervised clustering of CD3 + and CD8 + T-cell densities identified three major subgroups corresponding to the immune desert (137 patients), immune excluded (220 patients) and immune inflamed phenotypes (133 patients). Survival analysis revealed a particular poor prognosis for the immune desert phenotype for OS (0.0071) and PFS (0.0027). Conclusions: This study demonstrates a prognostical relevance of the immunphenotype and the distribution of CD3+ T-cells in vulvar cancer. Their value for therapeutic decision making has to be determined in the future.
Heart Failure With Preserved Ejection Fraction: Heterogeneous Syndrome, Diverse Preclinical Models
Authors: Jason Roh, Joseph A. Hill, Abhilasha Singh, María Valero-Muñoz, Flora Sam
Journal: Circulation Research (2022)

Heart failure with preserved ejection fraction (HFpEF) represents one of the greatest challenges facing cardiovascular medicine today. Despite being the most common form of heart failure worldwide, there has been limited success in developing therapeutics for this syndrome. This is largely due to our incomplete understanding of the biology driving its systemic pathophysiology and the heterogeneity of clinical phenotypes, which are increasingly being recognized as distinct HFpEF phenogroups. Development of efficacious therapeutics fundamentally relies on robust preclinical models that not only faithfully recapitulate key features of the clinical syndrome but also enable rigorous investigation of putative mechanisms of disease in the context of clinically relevant phenotypes. In this review, we propose a preclinical research strategy that is conceptually grounded in model diversification and aims to better align with our evolving understanding of the heterogeneity of clinical HFpEF. Although heterogeneity is often viewed as a major obstacle in preclinical HFpEF research, we challenge this notion and argue that embracing it may be the key to demystifying its pathobiology. Here, we first provide an overarching guideline for developing HFpEF models through a stepwise approach of comprehensive cardiac and extra-cardiac phenotyping. We then present an overview of currently available models, focused on the 3 leading phenogroups, which are primarily based on aging, cardiometabolic stress, and chronic hypertension. We discuss how well these models reflect their clinically relevant phenogroup and highlight some of the more recent mechanistic insights they are providing into the complex pathophysiology underlying HFpEF.
ProANP31-67 ameliorates adverse cardiac remodeling and improves systolic and diastolic functions in a preclinical model of cardiorenal syndrome
Authors: GJJ Silva, R Parvan, X Shen, M Frisk, R Altara, ME Strand, KB Rypdal, IG Lunde, WE Louch, JM Aronsen, K-O Stenslokken, MK Stokke, A Cataliotti
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority (HSØ-RHF, Project No. 25674) Background The cardiac hormone proANP31-67, a linear fragment of the N-terminal Atrial Natriuretic Peptide, has known enhancing renal effects. More recently, we described the cardio protective effects of this hormone in a model of chronic hypertension. More specifically, independently of the blood pressure level, proANP31-67 improved diastolic function, attenuated cardiac fibrosis, and reduced hypertrophy. Purpose The current study was designed to assess the cardiorenal effects of proANP31-67 in a rodent model of hampered renal function, followed by cardiac injury produced by ischemia/reperfusion (I/R). Methods Right uninephrectomy (UNX) was performed in Wistar rats (n=28). Sixteen weeks after UNX, rats underwent cardiac I/R injury and randomly assigned to proANP31-67 (50 ng/kg/day s.c., n=15) or Vehicle (n=13) for four weeks post I/R. Echocardiographic examinations were performed at baseline (before UNX), 16 weeks after UNX, and four weeks after I/R. At the end of the study, cardiomyocytes were isolated and tissue samples were collected. Results Chronic UNX resulted in diastolic impairment (E/A: 1.47±0.08 at baseline vs 0.98±0.14 at 16 wks post UNX, p=0.0010). I/R further accentuated the development of the cardiorenal syndrome, and induced a mild systolic dysfunction in the placebo treated animals. However, four weeks of treatment with proANP31-67 preserved systolic function (EF: 62±3% placebo vs 74±2% proANP31-67, p&amp;lt;0.0001), and reverted the diastolic dysfunction (E/A: 0.72±0.15 placebo vs 1.24±0.11 proANP31-67, p=0.0134). ProANP31-67 ameliorated the adverse cardiac remodeling (i.e., reduction in the cardiomyocyte cross-sectional area and interstitial fibrosis), enhanced Ca2+ handling, and improved cardiomyocyte t-tubules´ structural changes compared to vehicle. At the cellular level, in vitro experiments demonstrated the direct effect of proANP31-67 on cardiomyocyte hypertrophy (assessed by [3H]-leucine incorporation) induced by endothelin 1 and angiotensin II. Conclusion ProANP31-67 has a direct cardiomyocyte protective effect, leading to an improvement in Ca2+ homeostasis and t-tubules´ structures and, prevents the development of systolic and diastolic dysfunction in a pre-clinical model of cardiorenal syndrome.
Issues and Events
Journal: Diabetes Care (2022)

The 82nd annual American Diabetes Association Scientific Sessions will be held in New Orleans, Louisiana, on 3-7 June 2022, at the Ernest N. Morial Convention Center.The largest of its kind, this meeting brings together scientists and health care professionals from around the world who are involved in diabetes research and care.Attendees choose from thousands of original presentations given by leading experts in the field.The American Diabetes Association is currently planning a hybrid event.For more information, please visit professional.diabetes.org/scientific-sessions.
Circulating nucleosomes to identify non-smoker subjects at risk of lung cancer and triage them for low-dose CT scan.
Authors: Tung-Ming Tsai, Nathalie Hardat, Dorian Pamart, Marielle Herzog, Jin-Shing Chen
Journal: Journal of Clinical Oncology (2022)

e20558 Background: Lung cancer (LC) is the leading cause of cancer death worldwide and the most frequently occurring in men and the second most diagnosed cancer in woman after breast cancer. The primary risk factor leading to LC is tobacco smoke. Nevertheless, several studies in the US, UK and Asia reported an increasing rate of LC in non-smokers. 15-20% of LC patients worldwide are non-smokers with this percentage rising to 60% in non-smoking women in Asia. Current LC screening guidelines recommend a CT scan only for high-risk smokers. Despite there being no guidelines to recommend LC screening in non-smokers those with increased risk factors could be monitored. Therefore, a blood-test could offer a simple way to identify non-smokers at high-risk of LC and triage them to go for low-dose CT scan. Methods: We measured circulating levels of nucleosomes and CEA in 722 non-smoker subjects referred for CT scan at National Taiwan University Hospital. The patients were later confirmed to have either a LC (n = 509, including 401 patients at stage 0-1), non-malignant nodules (n = 142), or no-nodules (n = 71). Whole blood was collected in EDTA plasma tubes for analysis by six different Nu.Q chemiluminescent magnetic microparticle immunoassays (Belgian Volition SRL, Belgium) targeting H3.1-nucleosomes or different histone modifications (H3K9Me3-, H3K27Me3-, H3K36Me3-, H3K9Ac-, H3K14Ac-nucleosomes). CEA was analyzed on the Abbott ARCHITECT analyzer. We defined by logistic regression the best combination of biomarkers to identify LC cases in this non-smoking population in a rule-in approach. Results: At 95% specificity, none of the individual biomarkers exceed 24.8% of sensitivity for LC vs non-malignant nodules and no nodules. A combination of 2 nucleosome biomarkers: H3K9Me3- and H3K9Ac-nucleosomes with CEA in a logistic regression model showed improved sensitivity detecting 32.4% of LC in the non-smoker subjects at 95% specificity for LC vs non-malignant nodules and no nodules (area under the curve (AUC): 0.76, R 2 : 19.1%). In a non-smoking women sub-group by adding a third nucleosome biomarker: H3K36Me3-nucleosomes to the model we could detect 34.3% of the women who have lung cancer at 95% specificity (AUC: 0.75; R 2 : 20.2%). Conclusions: Our results indicate that a blood test combining circulating nucleosomes targeting different epigenetic modifications with CEA allow the detection of LC cases in a non-smokers population. This blood test could be part of the screening criteria for the non-smoking population at risk to develop LC and could help to triage them for low-dose CT scan.
Primary site and survival in chondrosarcoma: A National Cancer Database analysis.
Authors: Michael Burdyny, Connor Tupper, Vincent Eaton, Kevin McMahon, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2022)

e23503 Background: Chondrosarcoma is one of the most common primary malignancies of bone, accounting for around a fifth of all primary malignant bone tumors. These tumors typically affect the pelvis, hip, and shoulder but can arise anywhere that there is bone and cartilage (e.g. hands, feet, skull, etc.). To the authors’ knowledge, other primary sites have not been investigated in relation to its effect on survival outcomes. The aim of this study is to investigate this effect and see if there is any difference in survival amongst different primary sites in this patient population. Methods: Using the NCDB, patients diagnosed with chondrosarcoma between 2004-2018 were identified using ICD-O-3 histology codes 9220 and 9221. We analyzed the cohort to investigate survival outcomes in different primary sites. Univariate analysis was performed using SPSS to assess patient length of survival for each primary site. Statistical significance was set at α = 0.05. Results: A total of 7681 patients with known primary site that had survival data were included. The mean survival of the cohort was 140.3 months. The sites with the longest survival were the upper limb and the skull, face, and mandible, each of which had significantly longer survival than all other primary sites (all p &lt; .01). The lower limb and ribs, sternum, and clavicle had the next highest survival which was significantly longer than the vertebral column and pelvis, sacrum, and coccyx (all p &lt; .01). The vertebral column was the primary site with shortest survival with a median of 121 months. Conclusions: This study found significant survival differences between patients diagnosed with chondrosarcoma of different primary sites. Of all sites analyzed, the upper limb had the highest median survival of 187 months and showed statistical significance versus all other primary sites, and the vertebral column had the lowest median survival of 121 months. Future studies could be done regarding primary site to further elicit why there is such a large difference in survival, and can look at different imaging modalities used, time to treatment, and demographic and socioeconomic variables in each cohort.[Table: see text]
Pediatric Melatonin Ingestions — United States, 2012–2021
Authors: Karima Lelak, Varun Vohra, Mark I. Neuman, Michael S. Toce, Usha Sethuraman
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Melatonin is an endogenous neurohormone that regulates the sleep-wake cycle (1). It is used therapeutically for insomnia in adults and for primary sleep disorders in children (2). Melatonin is regulated by the Food and Drug Administration (FDA) as a dietary supplement. Various synthetic melatonin preparations are widely available over the counter (OTC) in the United States with sales increasing from $285 million in 2016 to $821 million in 2020 (3). Children are at increased risk for melatonin exposure because of the supplement's widespread use and growing popularity as a sleep aid. In 2020, melatonin became the most frequently ingested substance among children reported to national poison control centers (4); however, more research is needed to describe the toxicity and outcomes associated with melatonin ingestions in children. This study assessed isolated melatonin ingestions among the pediatric population (defined here as children, adolescents, and young adults aged ≤19 years) during January 1, 2012-December 31, 2021, using the American Association of Poison Control Centers' National Poison Data System (NPDS). During the 10-year study period, 260,435 pediatric melatonin ingestions were reported to NPDS, and the annual number of ingestions increased 530%. In addition, pediatric melatonin ingestions accounted for 4.9% of all pediatric ingestions reported to poison control centers in 2021 compared with 0.6% in 2012. Pediatric hospitalizations and more serious outcomes due to melatonin ingestions increased during the study period, primarily related to an increase in unintentional ingestions among children aged ≤5 years. Five children required mechanical ventilation, and two died. Consumers and health care professionals should be encouraged to report any melatonin product-related adverse events to MedWatch, the FDA's medical product safety reporting program. Public health initiatives should focus on raising awareness of increasing numbers of melatonin ingestions among children and on the development of preventive measures to eliminate this risk.
Rural-urban disparities in cancer mortality in the United States from 1999 to 2019.
Authors: Syed Hussaini, Amanda L. Blackford, Arjun Gupta
Journal: Journal of Clinical Oncology (2022)

6553 Background: U.S. cancer outcomes have improved in recent years, but it is unclear if these gains are realized in all geographic areas. We investigated US rural-urban disparities in age-adjusted cancer mortality rates (AAMRs) over a 20-year period. Methods: We identified cancer deaths from 1999 to 2019 in the CDC WONDER database. We classified populations into large metropolitan (≥1 million), small-or medium-sized metropolitan (50,000-999,999), and rural (&lt;50,000) areas based on the 2013 U.S. Census classification. We calculated annual AAMRs per 100,000 individuals and stratified results by age, sex, and race/ethnicity. We estimated annual percentage changes (APC) in AAMR using robust linear regression models of the log-scale AAMR, including population size as weights, and assessed differential changes over time by geographic area with interaction tests. Results: There were 12,935,840 deaths attributed to cancer (50% large metropolitan, 31.2% medium/small metropolitan, and 18.7% rural). AAMRs were highest in rural areas with least annual improvement. AAMR in large metropolitan areas decreased from 204.5 to 142.6 (APC -1.74 (95% CI [-1.78, -1.7])), and in rural areas it decreased from 209 to 168.3 (APC -1.05 (95% CI [-1.09, -1])) (P &lt;.001 for time trend). The absolute difference in AAMRs between large metropolitan and rural areas increased 5-fold, from 4.5 in 1999, to 25.7 in 2019. This trend was larger in elderly (&gt;65), where rural-urban disparity grew 25-fold (P &lt; 0.001). Non-Hispanic Blacks had higher AAMR than other racial/ethnic groups, and women had lower AAMR than men. Conclusions: In this national analysis of 20 years, rural residents suffered higher cancer mortality than their metropolitan counterparts resulting in widening disparities. Our findings inform program interventions possible through the recent reignition of the Cancer Moonshot in achieving geographic parity, and support ongoing congressional policy deliberations to increase access through re-investment in rural infrastructure.[Table: see text]
Geographic disparity between patients with multiple myeloma (non-Whites and Whites).
Authors: Christian S. Cheung, Nathan W. Sweeney, Thomas H. Molina, Jennifer M. Ahlstrom
Journal: Journal of Clinical Oncology (2022)

e20003 Background: People that live in rural areas experience significant health disparities from higher incidences of disease and disability, increased mortality rates, and lower life expectancies. Rural risk factors for health disparities include geographic isolation, lower socioeconomic status, limited access to healthcare specialists and sub-specialists, and limited job opportunities. Interestingly, we often see other, non-white, races experience delays in care, are under-treated, and lack of access to MM specialists. We, therefore, investigated whether there was a relationship between race and where one lives geographically. Methods: Validated real-world (RW) MM patient data was collected through HealthTree Cure Hub for Multiple Myeloma (healthtree.org). We examined the patient’s race which was either Caucasian American (White) or any other race (Black American, Asian, American Indian, East Indian, Middle Eastern, or Native Hawaiian) which was categorized as “non-White” and where they lived geographically (Rural, Urbanized Cluster, or Urban Areas). The association between race and geographic classification was compared by using a chi-squared test. Results: In this retrospective analysis of 2,687 MM patients, we compared the geographical classification of Whites (n = 2403) and non-Whites (n = 284). Our analysis revealed a significant association between the two groups and where they lived with a chi-square value of 20.455 (2, n = 2,687, p &lt; 0.001). We found that Whites are 1.9 times more likely to live in urbanized cluster areas and 2.7 times more likely to live in a rural area compared to non-Whites. Conclusions: The results of this RW analysis identified a disparity among races and where one lives geographically. While there is strong evidence of health disparities our findings revealed that where one lives geographically is not a probable reason why non-Whites experience delays in care, are under-treated, or lack access to MM specialists.